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Sugi, Kaoru; Kusano, Ayumu; Noro, Mahito; Numata, Ayaka; Tezuka, Naoki; Nakae, Takeshi; Sakai, Tsuyoshi; Kumagai, Kenta; Moriyama, Akiyoshi; Kujime, Shingo; Asayama, Tohru

doi:10.5105/jse.27.30

Cited by 4 publications

(1 citation statement)

References 3 publications

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“…First, the blood collection time included non-trough sampling. However, steady-state plasma bepridil concentration did not differ between 2 and 10 h after bepridil treatment [ 29 ] owing to its long half-life (48–80 h), suggesting that the time of blood collection had a minor effect on plasma bepridil concentrations. Second, because this study design was a retrospective observation, the effect of the edema, ascites, and urine volume on plasma bepridil concentrations could not be evaluated.…”

Section: Discussionmentioning

confidence: 99%

Effect of polypharmacy on plasma bepridil concentration in patients with heart failure: a multicenter retrospective study

Asai

Arihara

Omote

et al. 2023

J Pharm Health Care Sci

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Background Polypharmacy, defined as the concurrent use of over six drugs, is common in the treatment of heart failure (HF); however, unpredictable drug interactions with bepridil may occur. In this study, we have elucidated the influence of polypharmacy on plasma bepridil concentrations in patients with HF. Methods We conducted a multicenter retrospective study involving 359 adult patients with HF who received oral bepridil. Because QT prolongation is an adverse effect following plasma bepridil concentrations ≥800 ng/mL, the risk factors for patients achieving these concentrations at steady state were elucidated via multivariate logistic regression. The correlation between bepridil dose and plasma concentration was examined. The effect of polypharmacy on the value of the concentration-to-dose (C/D) ratio was investigated. Results A significant relationship was observed between bepridil dose and plasma concentration (p < 0.001), and the intensity of the correlation was moderate (r = 0.503). Based on multivariate logistic regression, the adjusted odds ratios for a daily dose of bepridil ≥1.6 mg/kg, polypharmacy, and concomitant of aprindine, a cytochrome P450 2D6 inhibitor, were 6.82 (95% coefficient interval: 2.104–22.132, p = 0.001), 2.96 (95% coefficient interval: 1.014–8.643, p = 0.047), and 8.63 (95% coefficient interval: 1.684–44.215, p = 0.010), respectively. Despite the moderate correlation in non-polypharmacy, the correlation was not observed in polypharmacy. Therefore, inhibiting metabolism, along with other mechanisms, may contribute to the polypharmacy-induced increase in plasma bepridil concentrations. Moreover, the C/D ratios in the groups receiving 6–9 and 10≤ concomitant drugs were 1.28- and 1.70-fold higher than in those receiving <6 drugs, respectively. Conclusions Plasma bepridil concentrations may be influenced by polypharmacy. Moreover, the plasma bepridil concentration increased in correlation with the number of concomitant drugs used. Although the mechanism of this increase could not be determined, plasma bepridil concentrations should be periodically monitored for safe use in patients with HF. Trial registration Retrospectively registered.

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Section: Discussionmentioning

confidence: 99%

Effect of polypharmacy on plasma bepridil concentration in patients with heart failure: a multicenter retrospective study

Asai

Arihara

Omote

et al. 2023

J Pharm Health Care Sci

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The use of serum bepridil concentration as a safe rhythm control strategy in patients with atrial tachyarrhythmias

Miura

Sumiyoshi

Tsuchiya

et al. 2012

Journal of Arrhythmia

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a b s t r a c tThe aim of this study was to evaluate the clinical significance of serum bepridil (Bep) concentration (SBC) for safely managing patients with atrial tachyarrhythmias (AT). Methods and results: SBC was measured in 37 patients with AT, including atrial fribrillation (AF) (31 cases), AF þ atrial flutter (AFL) (4 cases), AFL (1 case), and atrial tachycardia (1 case). The patients were administrated Bep for more than 4 weeks at the same dose. SBC was positively correlated with Bep dose per kilogram of body weight (p ¼0.015), QT interval (p¼ 0.019), and QTc (p ¼0.034). The patients were divided into 2 groups according to their SBC: the high-SBC (HSBC) group of 8 patients with an SBC Z 500 ng/ml and a low-SBC (LSBC) group of 29 patients with an SBC o 500 ng/ml. There was no difference in maintenance of sinus rhythm between the groups. For clinical variables, QT and QTc were significantly longer in the HSBC than in the LSBC group (p¼ 0.004 and p ¼ 0.016, respectively). Patients with QT 40.5 were more prominent in the HSBC group (37.5% vs. 3.4%, p¼ 0.026), and torsade de points (TdP) occurred in only one patient in the HSBC group. However, there were several patients with normal QT/QTc despite having high SBC. Conclusions: In patients treated with Bep, measurement of SBC is useful for preventing proarrhythmias.

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Clinical Outcome in Patients With Paroxysmal or Persistent Atrial Fibrillation Receiving Bepridil

Shiga

Suzuki

Naganuma

et al. 2011

Circ J

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Background: It is unknown whether bepridil improves cardiovascular events in atrial fibrillation (AF) patients, so this study evaluated the clinical outcome in paroxysmal or persistent AF patients receiving bepridil. Methods and Results:We conducted a cohort study of 284 consecutive patients who received bepridil for AF (25% female, 59±13 years) with a median follow-up period of 17 months (4-157 months). A total of 135 (48%) patients had structural heart disease, and 231 patients (81%) had previously received class I or class III antiarrhythmic drugs. The cumulative rates for cardiovascular events were 2.4%, 8.1%, and 10.1% at 1, 3, and 5 years, respectively. The cumulative rates for a composite of mortality, cerebral infarction, systemic embolism, major bleeding and heart failure were 9.7%, 18.2%, and 29.6% at 1, 3, and 5 years, respectively. The probability of progression to permanent AF was 23.5% at 5 years. Sudden death occurred in a patient with a prior myocardial infarction who was taking 200 mg daily, and torsade de pointes (Tdp) occurred in two patients without structural heart disease taking 200 mg daily. Excessive corrected QT interval prolongation (>0.50 s) was observed when plasma concentrations were higher than 800 ng/ml. Conclusions:Bepridil might not improve the clinical outcome in refractory AF patients. Bepridil-related adverse events, including QT prolongation and Tdp, occurred in a dose- and concentration-dependent manner. (Circ J 2011; 75: 1334 - 1342

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Cited by 4 publications

References 3 publications

Effect of polypharmacy on plasma bepridil concentration in patients with heart failure: a multicenter retrospective study

Effect of polypharmacy on plasma bepridil concentration in patients with heart failure: a multicenter retrospective study

The use of serum bepridil concentration as a safe rhythm control strategy in patients with atrial tachyarrhythmias

Clinical Outcome in Patients With Paroxysmal or Persistent Atrial Fibrillation Receiving Bepridil

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